Role of the bed nucleus of the stria terminalis in the acquisition of contextual fear at long or short context-shock intervals.

Rats received N-methyl-D-aspartate lesions of the bed nucleus of the stria terminalis (BNST) and then 10 aversive conditioning trials in which exposure to a context was paired with footshock. For half the animals, shock was presented 1 min after the onset of each context exposure; for the other half, shock was presented after 10 min. With the 1-min context duration, aversive conditioning (measured by freezing) was unaffected by BNST lesion. In contrast, at the 10-min duration, lesioned animals froze substantially less than sham controls. When 1-min-conditioned animals were left in the context for 10 min, freezing that was evident (though declining) throughout the test was not affected by the BNST lesion. When freezing over 10 min was similarly examined in the 10-min-conditioned animals, BNST lesions caused a deficit that was consistently evident over time. The results indicate that the BNST is involved in aversive conditioning to long-duration, but not merely contextual, conditional stimuli. Results may be less consistent with the view that BNST becomes activated after prolonged fear than the view that it is involved when a cue's onset has a remote temporal relation to shock.

PACAP in the BNST produces anorexia and weight loss in male and female rats.

Recent gene association studies have implicated pituitary adenylate cyclase-activating peptide (PACAP) systems in several psychiatric disorders associated with stressor exposure, and we have argued that many of the behavioral consequences of repeated stressor exposure may depend on the expression of PACAP in the bed nucleus of the stria terminalis (BNST). One behavioral consequence of the activation of stress systems can be anorexia and subsequent weight loss, and both the activation of central PACAP systems as well as neuronal activity in the BNST have also been associated with anorexic states in rodents. Hence, we investigated the regulation of food and water intake and weight loss following BNST PACAP infusion. BNST PACAP38 dose-dependently decreased body weight, as well as food and water intake in the first 24 h following infusion. Because different BNST subregions differentially regulate stress responding, we further examined the effects of PACAP38 in either the anterior or posterior BNST. Anterior BNST PACAP38 infusion did not alter weight gain, whereas posterior PACAP38 infusion resulted in weight loss. PACAP38 infused into the lateral ventricles did not alter weight, suggesting that the effects of BNST-infused PACAP were not mediated by leakage into the ventricular system. These data suggest that PACAP receptor activation in posterior BNST subregions can produce anorexia and weight loss, and corroborate growing data implicating central PACAP activation in mediating the consequences of stressor exposure.

Excitotoxic lesions of the bed nucleus of the stria terminalis (BNST) attenuate the effects of repeated stress on weight gain: evidence for the recruitment of BNST activity by repeated, but not acute, stress.

Exposure to repeated stress can lead to diverse and widespread behavioral consequences, including reduction in food and water intake and subsequent diminution in weight gain. Many reports have suggested that repeated stress substantially alters the neurochemistry, morphology and physiology of neurons within the bed nucleus of the stria terminalis (BNST). Here we investigate the role of the BNST in mediating the reduced weight gain observed during repeated stress. Rats exposed to a one-week variate stress paradigm exhibited a reduction in weight gain over the course of the 7-day paradigm. Excitotoxic lesions to a subregion of the anterolateral BNST containing the oval nucleus had no effects early in the 7-day paradigm, but significantly attenuated the effects of repeated stress on weight gain by the last day of stress. These data suggest that at least two mechanisms mediate the effects of stress on body weight gain, and that when stressor exposure becomes repeated, the BNST is recruited, worsening the symptoms of stressor exposure.